Alice Tsang Shaw, MD, PhD (Damon Runyon Fellow ‘04-‘05) of Massachusetts General Hospital, Boston, Pierre P. Massion, MD (Damon Runyon-Lilly Clinical Investigator ‘03-‘08) of the Vanderbilt University Medical Center, Nashville, and colleagues, reported the role of the ROS1 gene in certain non-small cell lung cancers (NSCLC).  1 to 2 percent of NSCLC tumors have mutations in ROS1.  Importantly, the researchers demonstrated that these ROS1-mutated tumors can be treated with the recently approved drug crizotinib, which also inhibits the growth of tumors containing mutations in the ALK gene.  These findings were demonstrated in vitro in cell lines, as well as in a single patient who displayed tumor shrinkage with a near complete response following crizotinib treatment.  The study was published in the Journal of Clinical Oncology.

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Maura L. Gillison, MD, PhD (Damon Runyon-Lilly Clinical Investigator ‘00-‘05) of the Ohio State University Comprehensive Cancer Center, Columbus, and colleagues reported that the prevalence of oral HPV (human papillomavirus) infection is about 7 percent in the United States.  The prevalence was higher among men than among women.  HPV-16, the high-risk strain linked to throat cancers and many cervical cancers, is detected in 1 percent of people.  The authors identified smoking and sexual behavior as risk factors for HPV infection.  The report was published in the Journal of the American Medical Association.

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Rachael A. Clark, MD, PhD (Damon Runyon Clinical Investigator ‘08-‘13) of Brigham and Women’s Hospital, Boston, and colleagues reported that the drug Campath (alemtuzumab) effectively treats patients with Leukemic cutaneous T-cell lymphoma (L-CTCL), a leukemia arising from a type of white blood cell called T-cells.  This cancer can involve the skin and other organs, and patients often die within three years.  The researchers demonstrated that Campath only kills T-cells that enter the bloodstream, including the cancerous T-cells; it spares a newly discovered population of immune cells called tissue resident T-cells that provide the patient with immunity against infections.  This study is the first demonstration in humans that tissue resident T-cells provide crucial immune protection of the skin.  The findings were published in the journal Science Translational Medicine.

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In two parallel studies, Ralph J. DeBerardinis, MD, PhD (Damon Runyon Clinical Investigator ‘11-‘14) of UT Southwestern Medical Center, Dallas, and Matthew G. Vander Heiden, MD, PhD (Damon Runyon-Rachleff Innovator ‘11-‘13, Fellow ‘06-‘08) of MIT, Cambridge, and colleagues, reported the use of noninvasive imaging technology (magnetic resonance spectroscopy) to visualize whether glioma brain tumors have a particular genetic mutation called IDH.  Several pharmaceutical companies are currently developing drugs that target IDH, with the goal of halting tumor growth. Knowing whether brain tumors have the IDH mutation will enable physicians to choose appropriate treatments and monitor whether potential drugs are effective.  These studies were published in the journals Nature Medicine and Science Translational Medicine, respectively.

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Catherine J. Wu, MD (Damon Runyon Clinical Investigator ‘07-‘12) and Matthew L. Meyerson, MD, PhD (Damon Runyon Fellow ‘95-‘98) of Dana-Farber Cancer Institute, Boston, led the first large-scale genomics study of chronic lymphocytic leukemia (CLL).  In tumor samples from 91 patients, they identified nine commonly mutated genes – five of which have been linked to CLL for the first time.  One of these genes, SF3B1, is required for gene splicing (RNA processing), connecting the process to disease progression.  The researchers found that mutation in SF3B1 may indicate a more aggressive form of the disease that requires prompt treatment.  These findings were published in the New England Journal of Medicine and presented at the American Society of Hematology annual meeting.

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David E. Lebwohl, MD (Damon Runyon Fellow ‘86-‘87) of Novartis, East Hanover, and colleagues, reported results of a Phase III clinical trial testing the treatment combination of everolimus (Afinitor), which blocks a protein known to affect blood vessel growth in cancer cells, and the hormone therapy exemestane (Aromasin).  724 metastatic breast cancer patients with hormone receptor-positive tumors were enrolled in the trial.  Patients who received the combination survived progression-free for twice as long as those who only received exemestane (7.4 months vs. 3.2 months).  The study was published in the New England Journal of Medicine.

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Ralph J. DeBerardinis, MD, PhD (Damon Runyon Clinical Investigator ‘11-‘14) of UT Southwestern Medical Center, Dallas, and colleagues, discovered a metabolic pathway unique to some tumors.  The tumor-specific pathway is dependent on the amino acid glutamine and reverses many of the chemical reactions of the Krebs cycle, used by normal cells.  This new finding could provide a new target for drugs that could specifically target cancer cells without harming healthy cells.  The study was published in the scientific journal Nature.

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Mark A. Lemmon, PhD (Damon Runyon Scholar ‘97-‘98, Damon Runyon Fellow ‘93-‘96) of University of Pennsylvania, Philadelphia, and colleagues, reported new findings that will allow physicians to identify which neuroblastoma patients are most likely to respond to crizotinib (Xalkori).  The drug was recently approved for treatment of certain lung cancers.  It targets a protein called anaplastic lymphoma kinase (ALK) which is mutated in about ten percent of children with deadly neuroblastoma tumors.  The researchers reported that these patients respond differently to treatment, depending on the particular mutation in ALK.  The drug blocked growth of neuroblastoma cells with the most common mutation, while tumor cells with a separate ALK mutation were more resistant to the drug.  These resistant cells, however, responded to a higher dosage of crizotinib.  The researchers are now conducting a clinical trial to determine the appropriate drug dose in children, potentially providing a safer and more effective treatment option than conventional chemotherapy.  The study was published in the journal Science Translational Medicine.

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Naoko Kobayashi, PhD (Damon Runyon Fellow ‘91-‘94) and colleagues at University of California, Los Angeles, reported results of a short-term Phase II clinical trial demonstrating anti-cancer benefits of fish oil.  Men who ate a low-fat diet with fish oil supplements for four to six weeks before having their prostate removed had slower cancer cell growth in their prostate tissue than men who ate a typical high-fat Western diet.  The researchers plan to expand this study to a larger group of men who will be monitored over an extended period of time (one year).  This initial study, published in the journal Cancer Prevention Research, suggests that altering the diet may favorably affect the biology of prostate cancer.

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A team of researchers including Wendy S. Garrett, MD, PhD (Damon Runyon Fellow ‘06-‘09), Matthew L. Meyerson, MD, PhD (Damon Runyon Fellow ‘95-‘98), Akinyemi I. Ojesina, MBBS, PhD (Damon Runyon Fellow ‘08-‘11) and Ramesh A. Shivdasani, MD, PhD (Damon Runyon Scholar ‘98-‘99) at Dana-Farber Cancer Institute and the Broad Institute, Cambridge, reported high levels of a specific type of bacteria, Fusobacterium, in colorectal tumor samples.  Future studies will focus on determining the connection between the bacterium and cancer.  If there is a link to disease development, the bacterium may be important for diagnosis, prevention and/or treatment.  The study was published in the journal Genome Research. 

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Judith Lieberman, MD, PhD (Damon Runyon Fellow ‘84-‘86) of the Immune Disease Institute and Harvard Medical School, Boston, and colleagues, reported the first description of competing endogenous RNAs (ceRNAs) and their function.  ceRNAs comprise a complex regulatory network that controls gene expression through binding of other RNAs called microRNAs.  This study demonstrated that PTEN, a tumor suppressor, is regulated by 150 ceRNAs in human prostate and colon cancer cell lines.  A separate study linked ceRNA-mediated regulation of PTEN to glioblastoma brain cancer.  The discovery provides a new understanding of the genetics underlying cancer.  These results were published in the journal Cell. 

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Julien Sage, PhD (Damon Runyon Scholar ‘05-‘07) of Stanford University, Stanford, and colleagues, reported a crucial role for Hedgehog signaling in the development of small-cell lung cancer (SCLC).  They demonstrated that blocking Hedgehog signaling inhibited the growth of SCLC, particularly after chemotherapy.  Their findings suggest that Hedgehog pathway inhibition may be a promising therapeutic strategy to slow disease progression and delay cancer recurrence in SCLC patients.  This study was published in the journal Nature Medicine.

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Ralph M. Steinman, MD (Damon Runyon Clinical Investigator Mentor) of The Rockefeller University, New York, received the Nobel Prize in Physiology or Medicine 2011 “for his discovery of the dendritic cell and its role in adaptive immunity.”  His work revealed new insights into how infections, cancer, and inflammatory diseases can be prevented and treated.  Dr. Steinman passed away on September 30 at the age of 68.

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The intent of the NIH High-Risk Research Awards is to encourage investigators to explore bold ideas that have the potential to catapult fields forward and speed the translation of research into improved health.  We congratulate the Damon Runyon scientists who are recipients of these awards.

Pioneer Award:
Brenda L. Bass, PhD (Fellow ‘85-‘88), University of Utah, Salt Lake City
William M. Clemons, PhD (Fellow ‘02-‘04), California Institute of Technology, Pasadena
Tao Pan, PhD (Fellow ‘91-‘93), University of Chicago, Chicago

New Innovator Award:
Heather R. Christofk, PhD (Innovator ‘10-‘12), University of California, Los Angeles
Lea A. Goentoro, PhD (Fellow ‘07-‘10), California Institute of Technology, Pasadena

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Peter S. Nelson, MD (Clinical Investigator Mentor, Damon Runyon Scholar ‘02-‘04) of Fred Hutchinson Cancer Research Center, Seattle, and colleagues, conducted the first comprehensive assessment of the genome of advanced, lethal prostate cancer.  They discovered a number of recurrent genetic mutations common to advanced prostate cancer that may contribute to disease progression and resistance to commonly used therapies.  The researchers hope that these findings will lead to development of new strategies for diagnosis and treatment.  The study was published in the Proceedings of the National Academy of Sciences.

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President Obama named Rudolf Jaenisch, MD (Fellowship Sponsor) of the Whitehead Institute for Biomedical Research and Massachusetts Institute of Technology, Cambridge, one of seven recipients of the National Medal of Science, the nation’s highest scientific honor.  Awarded annually, the Medal recognizes individuals who have made outstanding contributions to science and engineering.  

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Scott A. Armstrong, MD, PhD (Damon Runyon-Lilly Clinical Investigator ‘03-‘08) of Dana-Farber Cancer Institute and Children’s Hospital Boston, and Kornelia Polyak, MD, PhD (Clinical Investigator Award Committee Member) of Dana-Farber Cancer Institute, Boston, are two of this year’s recipients of the Paul Marks Prize for Cancer Research.  The awards recognize three young investigators under the age of forty-six for their exceptionally innovative work that has helped to advance the field of cancer research.  Dr. Armstrong is recognized for notable achievements in the fields of cancer stem cell research and genomics that have led to landmark findings pointing to potential new therapies for leukemia.  Dr. Polyak is recognized for her pioneering genomic discoveries in normal and cancerous breast tissue and for her efforts to translate those findings into improved diagnostic and therapeutic approaches.

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James E. Bradner, MD (Damon Runyon-Rachleff Innovator ‘11-‘13) of the Dana-Farber Cancer Institute, Boston, and colleagues, identified the protein Brd4 as a critical requirement for acute myeloid leukemia (AML) disease maintenance.  Brd4 functions to control expression of Myc, a protein frequently disrupted in many cancers.  Blocking Brd4, using either RNA interference or a drug called JQ1, led to anti-leukemic effects such as cancer cell death and a delay in disease progression.  These findings were published in the journal Nature.   In a second paper published in the journal Cell, Bradner and colleagues reported the additional success of JQ1 in stopping the growth of multiple myeloma cells, which are dependent on Myc.  These studies establish inhibition of Brd4 as a promising therapeutic strategy in multiple cancers. 

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Ramesh A. Shivdasani, MD, PhD (Damon Runyon Scholar ‘98-‘99) of Dana-Farber Cancer Institute, Boston, and colleagues discovered a mechanism for how cancer cells become resistant to cetuximab/Erbitux, which is used to treat colorectal cancer or squamous cell cancer of the head and neck. They reported that a protein called ERBB2 allows cells to remain unresponsive to the drug. The study suggests that combining cetuximab with ERBB2-inhibiting drugs could be an effective therapy to both heighten and/or restore the drug’s potency. These findings were published in the journal Science Translational Medicine. 

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